In recent years, saccharide-containing compounds and saccharide-like compound have attracted attention as useful physiologically active substances in the field of fine chemicals such as medicines and agricultural chemicals. As one of such saccharide-like compounds, known is (2S, 4S)-2-hydroxy-4-hydroxymethyl-4-butanolide (3-DPA-lactone) of chemical structure of formula (V) given below: ##STR1##
The compound 3-DPA-lactone is present in the body fluid of an animal. An increase in the concentration of the compound in the blood is observed in a hungry rat. Also, an ingestive action or appetite is induced by the administration of the compound. Such being the situation, 3-DPA-lactone is known as an endogenous appetite-promoting substance, as described in "H. Ohmura, N. Shimizu (Kagaku to Seibutsu), Vol. 22, No. 4, page 228, and its reference article, O. Uchikawa, N. Okukado, T. Sakata, K. Arase, Bull. Chem. Soc. Jpn., 61, 2025 (1988)".
Thus, 3-DPA-lactone is indispensable for the scientific clarification of the ingestive action of animals including human beings. It is possible to widely apply the clarified mechanism for the development of food, medicines and agricultural chemicals. It is also possible to promote the growth of livestock by adding an appetite-promoting substance to the feed for the livestock and using its appetite-promoting effect.
Only traces of 3-DPA-lactone are present in nature, making it difficult to obtain a large amount of the compound by extraction from natural materials. In other words, it is necessary to employ a synthetic technique for obtaining a large amount of 3-DPA-lactone.
Presently, a method of manufacturing 3-DPA-lactone, in which L-malic acid having an optical activity is used as the starting material, is known to the art, as described in "0. Uchikawa, N. Okukado, T. Sakata, K. Arase, K. Terada, Bull. Chem. Soc. Jpn., 61, 2025 (1988)". Also known is a method using .gamma.-ribonolactone as the starting material, as described in "K. Bock, I. Lundt, C. Pedersen, Acta. Chem. Scand., B85, 155 (1981)". In the known method using L-malic acid as the starting material, a vinyl group is introduced by Grignard reaction to the carbonyl group of (S)-3,4-0-isopropylidene-3,4-dihydroxy butanal so as to form a hydroxyl group at the 2-position of 3-DPA-lactone, followed by cleaving the vinyl group in an oxidizing manner by Sharpless method so as to form a carboxyl group and, thus, to form .gamma.-lactone.
However, the Grignard reaction employed in the known method described above is not stereoselective, with the result that two kinds of diastereomers are formed with respect to the hydroxyl group at the 2-position. Naturally, it is necessary to separate these diastereomers after the lactone formation, with the result that the yield of the desired product in which an S-arrangement is formed with respect to the carbon atom at the 2-position is as low as about 30%.
In addition, as many as six process steps are required for preparing the direct starting material of hydroxy aldehyde itself having an optical activity from L-malic acid, and the yield thereof is only 25%. It follows that as many as 11 process steps are required for manufacturing 3-DPA-lactone from L-malic acid. Further, if the removal of one diastereomer is taken into account, the total yield is as low as only about 4%.
In the known method using .gamma.-ribonolactone as the starting material, the hydroxyl group of .gamma.-ribonolactone is protected by an acetyl group, followed by applying a catalytic hydrogenation under a high pressure in the presence of palladium-carbon as a catalyst so as to achieve deacylation and, thus, to refine 3-DPA-lactone. In this method, however, it is necessary to carry out the catalytic hydrogenation under such a high pressure as 100 atms., making it necessary to use a complex apparatus. In addition, a problem remains unsolved in terms of safety.